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PRIORITY PRESS - 2012 Canadian Hypertension Congress

Toronto, Ontario / October 25-28, 2012

Toronto - Over 1000 patients in Canada are diagnosed with hypertension each day. Best treatment plan depends on factors including severity of high blood pressure (BP), age, comorbidities, as well as, patient and physician preference. Common to all antihypertensive drug regimens is the goal of getting patients to target BP quickly, while reducing pill burden. Most patients, especially those with diabetes, usually require 2 or 3 different drug classes to achieve BP goals, it is therefore important for physicians to simplify adherence requirements with single-pill combinations favouring agents with more potent BP-lowering effects to optimize compliance and outcome. The trend of combining an angiotensin II receptor blocker (ARB) with a diuretic into a single-tablet has gained momentum in hypertension therapy. Insights into the relative efficacy of a long-acting ARB combined with a potent diuretic to improve BP control and provide greater adherence was discussed.

Chief Medical Editor: Dr. Léna Coïc, Montréal, Quebec

Much progress has been made by Canadian physicians since the nationwide Heart Health Survey in the early 1990s, where only 13% of patients with hypertension were well controlled. Recently, the Canadian Health Measurement Survey showed that approximately two-thirds of hypertensive patients are now achieving target blood pressure (BP) levels, a testimony to widespread recognition that uncontrolled BP is a major risk factor for cardiovascular (CV) disease, chronic kidney disease and heart failure.

That being said, as Dr. Ellen Burgess, Professor of Medicine, University of Calgary, told delegates, “There are still a lot of care gaps.” One of these is getting both young individuals and men into the office early enough to be treated before target organ damage develops. Another is “therapeutic inertia” i.e. waiting too long to modify the BP treatment regimen when patients are not at goal.

Lifestyle Change: A Critical Component

According to CHEP (Canadian Hypertension Education Program) recommendations, the management of hypertension is about global CV risk management and vascular protection. In addition, lifestyle modifications are the cornerstone of both antihypertensive and antiatherosclerotic therapy demonstrating their positive impact on BP reduction.

However, waiting for patients to embrace healthy lifestyle changes before initiating treatment qualifies as therapeutic inertia. “If patients come in after a month and they have not taken a single step towards modifying whatever it was they were supposed to modify, it is not going to happen,” Dr. Burgess remarked. Conversely, if they have made an effort to modify their life style—showing weight loss, reduced alcohol consumption, starting to exercise more—physicians may explain to their patients started on medication that if they are successful with their lifestyle change, “medication can be stopped providing there has been good solid BP control for about year and a half. About half of those patients will be able to remain off therapy,” she also noted.

If a patient has been started on antihypertensive therapy, it is important to note that the maximum effect from most agents is achieved within 2 weeks of initiation and 6 weeks for a diuretic, Dr. Burgess explained in an interview. “In other words, we are not going to get more out of a drug if we drag it out for another month or 2,” she remarked. Results from the VALUE (Valsartan Antihypertensive Long-term Use Evaluation) trial underscore how important it is to get to target BP quickly, (Lancet 2004;363:2022-31) where small differences in BP in the early course of that trial resulted in important differences in cause-specific outcomes in high-risk patients, she added.

Achieving Greater Rates of BP Control with Single-pill Combinations

Making sure the regimen is as convenient as possible makes a difference in getting patients to goal more quickly and effectively. In a study cited by Dr. Phil McFarlane, Lecturer, University of Toronto, Feldman et al. compared a simplified treatment algorithm consisting of initial fixed-dose combination of a diuretic with a low-dose angiotensin converting enzyme (ACE) inhibitor or an angiotensin II receptor blocker (ARB) to the standard approach recommended by the CHEP guidelines (Hypertension 2009;53:646-53).

At 6 months follow-up, almost 65% of patients on the simplified treatment algorithm had achieved BP targets compared to approximately 53% treated according to CHEP guidelines (P=0.026). Change in BP was also greater at 22.6 mm Hg in the simplified algorithm arm compared with 17.5 mm Hg for their CHEP counterparts. “CHEP tells us that if you pick 2 medications for a patient and they happen to be available in a fixed-dose, use the fixed-dose combination,” Dr. McFarlane emphasized, “and even though patients know they are on the exact same amount of drug as they were before, somehow going from 2 tablets to 1 makes them feel they are getting better,” improving compliance.

Treatment Optimization

Optimizing antihypertensive efficacy within a given drug class is also an underused tactic to get patients to goal. In another study cited by Dr. McFarlane (Hypertension 2006;47:352-8), Ernst et al. reported that at week 8, there was a greater reduction in mean 24-hour ambulatory systolic BPs (SBPs) from baseline with chlorthalidone 25 mg/day (12.4 mm Hg) vs. hydrochlorothiazide (HCTZ) 50 mg/day (7.4 mm Hg). Nighttime mean reductions were also significantly greater with chlorthalidone at 13.5 mm Hg (P<0.05) compared with 6.4 mm Hg for HCTZ.

There is also increasing evidence that the newer generation ARBs are significantly more effective at reducing BP than the older renin-angiotensin system (RAS) inhibitors. Citing combined study results, Dr. McFarlane noted that at the end of a 6-week, randomized control trial in mild to moderate hypertension, azilsartan 80 mg/day reduced ambulatory SBP to a significantly greater degree (15.3 mm Hg) than ramipril 10 mg/day (11.3 mm Hg). In another study, the same azilsartan dose reduced 24-hour mean ambulatory SBP by 21.2 mm Hg at the end of 6 weeks compared to 12.2 mm Hg with valsartan 320 mg/day.

Another randomized controlled trial compared the single-pill combination of the long-acting ARB azilsartan and chlorthalidone to azilsartan given concomitantly with HCTZ. At 6 weeks, a greater mean reduction in SBP for the single-pill combination chlorthalidone/azilsartan (35.1 mm Hg) was reported when compared with the concomitant administration of azilsartan + HCTZ (29.5 mm Hg) (Am J Med 2012;Epub ahead of print, August 29).

Some 64% of patients on the single-pill combination also achieved target BP goals at week 6 compared with approximately 46% on the azilsartan + HCTZ (P<0.001). Drug discontinuations due to adverse events were not different between the 2 groups, as investigators noted.

“Polypharmacy complicates patient care—we have to worry about drug-drug-interactions and they have to worry about adherence, so fixed-dose combinations and optimization of the selection of medication within drug classes can help patients get to target and minimize their pill count,” Dr. McFarlane told delegates.

Simplifying Polypharmacy

Minimizing pill burden is particularly important in hypertensive patients with co-morbid conditions, such as diabetes, which in itself requires multiple drugs to control.

Dr. Pavel Hamet, Professor of Medicine, Université de Montréal, Quebec, reminded delegates that 75% of patients with diabetes are hypertensive as well. “In diabetes, hypertension is always more difficult to treat and patients always need more medication.” Because patients with diabetes are at higher risk, controlling hypertension in this patient population has significant CV benefit. The lower BP targets than non-diabetic patients permits better protection against not only CV events but stroke, retinopathy and progressive renal failure. For example, in the HOT trial, CV events were significantly lower at study end point at 11.9 per 1000 patient-years in those who achieved the lowest BP targets compared to those whose BPs were the highest at 24.4 events per 1000 patient-years (P<0.005).

Dr. Hamet noted that hypertensive patients with diabetes on average need at least 3 drugs to achieve recommended BP targets of <130/80 mm Hg. Barring contraindications, most patients with diabetes should be on some form of RAS inhibition, a diuretic and a long-acting calcium channel blocker.

Dr. Hamet expressed his support for fixed-combinations of agents for hypertensive patients with co-morbidities as they reduce the number of pills taken and increase compliance. “So if you can decrease the pill count, that will help.”

Summary

Many hypertensive patients, particularly those with comorbid conditions, are on an impressive array of medications, making adherence to the regimen difficult at best. Fortunately, there is now an equally impressive array of combination therapies in single-tablet formulations, which help simplify regimens. By choosing the most effective medication within an antihypertensive drug class, physicians may further reduce pill burden, facilitate adherence and improve BP control.